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SGI-1776 CAS: 1025065-69-3

Category: Inhibitors
Product Name: SGI-1776
Cat No: I000164
CAS No: 1025065-69-3
Synonyms: N-[(1-methylpiperidin-4-yl)methyl]-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazin-6-amine
Molecular Formula: C20H22F3N5O
Molecular Weight: 405.4
SMILES: CN1CCC(CNC(C=C2)=NN3C2=NC=C3C4=CC=CC(OC(F)(F)F)=C4)CC1
InChI: None
InChIKey: MHXGEROHKGDZGO-UHFFFAOYSA-N
Solubility: 10 mM in DMSO
Target: Pim
IC50: 7 nM [1]
Storage: powder
CAS 1025065-69-3,SGI-1776
  • Description

SGI-1776 is a novel ATP competitive inhibitor of Pim1 with IC50 of 7 nM; 50- and 10-fold selective versus Pim2 and Pim3, also potent to Flt3 and haspin.
IC50 value: 7 nM [1]
Target: Pim1
in vitro: In addition to Pim, SGI-1776 also potently targets FLT3 (IC50 = 44nM). Treatment of AML cells with SGI-1776 results in a concentration-dependent induction of apoptosis. Importantly, SGI-1776 is also cytotoxic in AML primary cells, irrespective of FLT3 mutation status and results in Mcl-1 protein decline [1]. Treatment of CLL cells with SGI-1776 results in a concentration-dependent induction of apoptosis. SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction. Apoptosis induction coupled with the inhibition of RNA synthesis is observed in CLL cells treated with SGI-1776 [2]. SGI-1776 exhibites cytotoxic activity in vitro with a median relative IC50 of 3.1 mM. SGI-1776 induces tumor growth inhibition meeting criteria for intermediate EFS T/C activity in 1 of 39 evaluable models. In contrast, SGI-1776 induces complete responses of subcutaneous MV4;11 [3].
in vivo: Consistent with cell line data, xenograft model studies with mice bearing MV-4-11 tumors shows efficacy with SGI-1776. [1] SGI-1776 has shown preclinical activity against leukemia and solid tumor cell line models with IC50 values of 0.005–11.68 mM. SGI-1776 induces significant differences in EFS distribution in vivo in 9 of 31 solid tumor xenografts and in 1 of 8 of the evaluable ALL xenografts [3].

  • Spec

Appearance:white solid powder
Purity: > 98%

  • References


1:Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776. Hou X, Yu Y, Feng J, Wang J, Zheng C, Ling Z, Ge M, Zhu X.Exp Cell Res. 2017 Mar 15;352(2):403-411. doi: 10.1016/j.yexcr.2017.02.029. Epub 2017 Feb 20. PMID: 28228352 Free Article
2:The novel anti-adipogenic effect and mechanisms of action of SGI-1776, a Pim-specific inhibitor, in 3T3-L1 adipocytes. Park YK, Hong VS, Lee TY, Lee J, Choi JS, Park DS, Park GY, Jang BC.Int J Mol Med. 2016 Jan;37(1):157-64. doi: 10.3892/ijmm.2015.2415. Epub 2015 Nov 19. PMID: 26719859
3:SGI-1776, an imidazo pyridazine compound, inhibits the proliferation of ovarian cancer cells by inactivating Pim-1. Xie J, Bai J.Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2014 Jul;39(7):649-57. doi: 10.11817/j.issn.1672-7347.2014.07.001. PMID: 25080901 Free Article
4:Combination of Pim kinase inhibitor SGI-1776 and bendamustine in B-cell lymphoma. Yang Q, Chen LS, Neelapu SS, Gandhi V.Clin Lymphoma Myeloma Leuk. 2013 Sep;13 Suppl 2:S355-62. doi: 10.1016/j.clml.2013.05.024. PMID: 24290221 Free PMC Article
5:Biological effects of the Pim kinase inhibitor, SGI-1776, in multiple myeloma. Cervantes-Gomez F, Chen LS, Orlowski RZ, Gandhi V.Clin Lymphoma Myeloma Leuk. 2013 Sep;13 Suppl 2:S317-29. doi: 10.1016/j.clml.2013.05.019. Epub 2013 Aug 27. PMID: 23988451 Free PMC Article
6:The Pim kinase inhibitor SGI-1776 decreases cell surface expression of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and drug transport by Pim-1-dependent and -independent mechanisms. Natarajan K, Bhullar J, Shukla S, Burcu M, Chen ZS, Ambudkar SV, Baer MR.Biochem Pharmacol. 2013 Feb 15;85(4):514-24. doi: 10.1016/j.bcp.2012.12.006. Epub 2012 Dec 19. PMID: 23261525 Free PMC Article
7:Transcription and translation are primary targets of Pim kinase inhibitor SGI-1776 in mantle cell lymphoma. Yang Q, Chen LS, Neelapu SS, Miranda RN, Medeiros LJ, Gandhi V.Blood. 2012 Oct 25;120(17):3491-500. doi: 10.1182/blood-2012-02-412643. Epub 2012 Sep 6. PMID: 22955922 Free PMC Article
8:The FLT3 and Pim kinases inhibitor SGI-1776 preferentially target FLT3-ITD AML cells. Hospital MA, Green AS, Lacombe C, Mayeux P, Bouscary D, Tamburini J.Blood. 2012 Feb 16;119(7):1791-2. doi: 10.1182/blood-2011-11-393066. No abstract available. PMID: 22343664 Free Article
9:Initial testing (stage 1) of SGI-1776, a PIM1 kinase inhibitor, by the pediatric preclinical testing program. Batra V, Maris JM, Kang MH, Reynolds CP, Houghton PJ, Alexander D, Kolb EA, Gorlick R, Keir ST, Carol H, Lock R, Billups CA, Smith MA.Pediatr Blood Cancer. 2012 Oct;59(4):749-52. doi: 10.1002/pbc.23364. Epub 2011 Nov 2. PMID: 22052829 Free PMC Article
10:Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Chen LS, Redkar S, Taverna P, Cortes JE, Gandhi V.Blood. 2011 Jul 21;118(3):693-702. doi: 10.1182/blood-2010-12-323022. Epub 2011 May 31. PMID: 21628411 Free PMC Article


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